Pub Date : 2026-02-10Epub Date: 2025-12-30DOI: 10.1016/j.ijpharm.2025.126548
Michela Piccinini , Chiara Suvieri , Maria Laura Belladonna , Donatella Pietrella , Alessandro Di Michele , Valeria Ambrogi , Morena Nocchetti
The development of biomaterials capable of promoting bone tissue regeneration while simultaneously exhibiting antimicrobial activity is a highly relevant and timely topic, both in healthcare and economic terms. The present study aimed to produce scaffolds based on a composite of hydroxyapatite (HA) and calcium carbonate (CaCO3) loaded with 2.5 and 5 wt% of gallium, known for its antimicrobial activity and only recently investigated for its potential to modulate bone metabolism. The characterization of the scaffolds, performed by X-ray powder diffraction, field emission scanning electron microscopy, and attenuated total reflectance Fourier transform infrared spectroscopy, shows a homogeneous distribution of gallium at the nanoscale and presence of tetracalcium diphosphate oxide beside HA and CaO. In vitro bioactivity test proved the growth of the new HA on the scaffolds after three days. Scaffolds were tested for their antibacterial activity against the gram-positive Staphylococcus aureus and Staphylococcus epidermidis, as well as for their ability to inhibit osteoclastogenesis.
The results showed that released gallium interferes with the differentiation of precursor cells into mature bone-resorbing osteoclasts and showed moderate antibacterial effects against the tested strains.
{"title":"Gallium-integrated HA/CaCO3 scaffold and its effect on gram-positive bacteria and osteoclastogenesis","authors":"Michela Piccinini , Chiara Suvieri , Maria Laura Belladonna , Donatella Pietrella , Alessandro Di Michele , Valeria Ambrogi , Morena Nocchetti","doi":"10.1016/j.ijpharm.2025.126548","DOIUrl":"10.1016/j.ijpharm.2025.126548","url":null,"abstract":"<div><div>The development of biomaterials capable of promoting bone tissue regeneration while simultaneously exhibiting antimicrobial activity is a highly relevant and timely topic, both in healthcare and economic terms. The present study aimed to produce scaffolds based on a composite of hydroxyapatite (HA) and calcium carbonate (CaCO<sub>3</sub>) loaded with 2.5 and 5 wt% of gallium, known for its antimicrobial activity and only recently investigated for its potential to modulate bone metabolism. The characterization of the scaffolds, performed by X-ray powder diffraction, field emission scanning electron microscopy, and attenuated total reflectance Fourier transform infrared spectroscopy, shows a homogeneous distribution of gallium at the nanoscale and presence of tetracalcium diphosphate oxide beside HA and CaO. In vitro bioactivity test proved the growth of the new HA on the scaffolds after three days. Scaffolds were tested for their antibacterial activity against the gram-positive <em>Staphylococcus aureus</em> and <em>Staphylococcus epidermidis</em>, as well as for their ability to inhibit osteoclastogenesis.</div><div>The results showed that released gallium interferes with the differentiation of precursor cells into mature bone-resorbing osteoclasts and showed moderate antibacterial effects against the tested strains.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126548"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2026-01-08DOI: 10.1016/j.ijpharm.2026.126583
Jiabi Ouyang , Goedele Craye , Chris Vervaet , Guy Van den Mooter
Pectin (PEC) and ethylcellulose (EC) are widely employed as colon-targeted coating materials due to their complementary properties, namely enzymatic degradability of pectin in the colonic environment and hydrophobicity of ethylcellulose. Beyond polymer selection, processing parameters critically influence the mass transfer characteristics of pharmaceutical coatings. This study investigated the relationship between the permeability of PEC-EC isolated films and drug release profiles of corresponding pellet coatings, prepared at a fixed polymer ratio but varied process conditions for the model drug theophylline. Manufacturing parameters including solid content of the polymer dispersion, film/coating thickness, atomization air pressure, and drying temperature were systematically adjusted. The resulting films and coatings exhibited significant variation in permeability coefficients and drug release rates. Higher dispersion viscosity and solid content, coupled with reduced spraying level, correlated with increased permeability and accelerated drug release. Notably, lower atomization air pressure enhanced film permeability but did not significantly affect drug release from coated pellets within the tested range. The observed discrepancy between sensitivity of the isolated films to changing manufacturing conditions and the robustness of the pellet coating process underscores the reliability of fluidized bed coating processes in achieving consistent drug release kinetics. These findings highlight the consistent influence of process parameters on transport properties and suggest that permeability testing of isolated films may serve as a predictive and cost-effective screening tool for optimizing coating formulations.
{"title":"Correlation between permeability of pectin-ethylcellulose films and drug release from coatings under variable processing conditions","authors":"Jiabi Ouyang , Goedele Craye , Chris Vervaet , Guy Van den Mooter","doi":"10.1016/j.ijpharm.2026.126583","DOIUrl":"10.1016/j.ijpharm.2026.126583","url":null,"abstract":"<div><div>Pectin (PEC) and ethylcellulose (EC) are widely employed as colon-targeted coating materials due to their complementary properties, namely enzymatic degradability of pectin in the colonic environment and hydrophobicity of ethylcellulose. Beyond polymer selection, processing parameters critically influence the mass transfer characteristics of pharmaceutical coatings. This study investigated the relationship between the permeability of PEC-EC isolated films and drug release profiles of corresponding pellet coatings, prepared at a fixed polymer ratio but varied process conditions for the model drug theophylline. Manufacturing parameters including solid content of the polymer dispersion, film/coating thickness, atomization air pressure, and drying temperature were systematically adjusted. The resulting films and coatings exhibited significant variation in permeability coefficients and drug release rates. Higher dispersion viscosity and solid content, coupled with reduced spraying level, correlated with increased permeability and accelerated drug release. Notably, lower atomization air pressure enhanced film permeability but did not significantly affect drug release from coated pellets within the tested range. The observed discrepancy between sensitivity of the isolated films to changing manufacturing conditions and the robustness of the pellet coating process underscores the reliability of fluidized bed coating processes in achieving consistent drug release kinetics. These findings highlight the consistent influence of process parameters on transport properties and suggest that permeability testing of isolated films may serve as a predictive and cost-effective screening tool for optimizing coating formulations.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126583"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2026-01-05DOI: 10.1016/j.ijpharm.2026.126572
Monika Wojtyłko , Tomasz Osmałek , Wiesław Kuczko , Radosław Wichniarek , Ariadna B. Nowicka , Mirosław Szybowicz , Dariusz T. Mlynarczyk , Anna Froelich , Barbara Jadach , Oliwia Kordyl , Irena Budnik , Antoni Białek , Julia Krysztofiak , Bozena Michniak-Kohn , Joanna Budna-Tukan , Andrzej Miklaszewski , Dimitrios A. Lamprou
Microneedles (MNs) are small devices that help to overcome the skin barrier and, thus, increase the effectiveness of transdermal drug delivery. This approach could be beneficial, especially for drugs characterised by low oral bioavailability, such as the antidepressant agomelatine (AGM), which is now only available on the market as an oral tablet. The aim of this study was to obtain agomelatine-loaded microneedle systems for potential use in the treatment of depression, using the 3D-printing methods. 3D-printing is an emerging technology enabling the manufacture of drug dosage forms or devices in a personalised, fast, and cost-efficient manner. Three 3D-printing techniques, different drug loading methods, and various shapes of microneedles were investigated along with the mechanical and physicochemical evaluation, release, stability, and toxicity studies of the obtained samples. Masked Stereolithography (MSLA) and PolyJet methods were successful in obtaining good-quality microneedle systems. Additionally, the MSLA method allowed for easy combining of the resin with the drug. The presence of the drug in the product was confirmed, and the drug release pattern depended on the loading method. Mechanical testing showed that Pyramid and Cone geometries were the most promising in puncture tests, and stability testing revealed the need for light- and moisture-resistant packaging. The formulations selected based on the obtained results will be further investigated on the way to create a transdermal alternative to agomelatine oral tablets and increase the effectiveness of depression treatment.
{"title":"Agomelatine 3D-printed microneedles as a potential drug delivery system for the treatment of depression","authors":"Monika Wojtyłko , Tomasz Osmałek , Wiesław Kuczko , Radosław Wichniarek , Ariadna B. Nowicka , Mirosław Szybowicz , Dariusz T. Mlynarczyk , Anna Froelich , Barbara Jadach , Oliwia Kordyl , Irena Budnik , Antoni Białek , Julia Krysztofiak , Bozena Michniak-Kohn , Joanna Budna-Tukan , Andrzej Miklaszewski , Dimitrios A. Lamprou","doi":"10.1016/j.ijpharm.2026.126572","DOIUrl":"10.1016/j.ijpharm.2026.126572","url":null,"abstract":"<div><div>Microneedles (MNs) are small devices that help to overcome the skin barrier and, thus, increase the effectiveness of transdermal drug delivery. This approach could be beneficial, especially for drugs characterised by low oral bioavailability, such as the antidepressant agomelatine (AGM), which is now only available on the market as an oral tablet. The aim of this study was to obtain agomelatine-loaded microneedle systems for potential use in the treatment of depression, using the 3D-printing methods. 3D-printing is an emerging technology enabling the manufacture of drug dosage forms or devices in a personalised, fast, and cost-efficient manner. Three 3D-printing techniques, different drug loading methods, and various shapes of microneedles were investigated along with the mechanical and physicochemical evaluation, release, stability, and toxicity studies of the obtained samples. Masked Stereolithography (MSLA) and PolyJet methods were successful in obtaining good-quality microneedle systems. Additionally, the MSLA method allowed for easy combining of the resin with the drug. The presence of the drug in the product was confirmed, and the drug release pattern depended on the loading method. Mechanical testing showed that Pyramid and Cone geometries were the most promising in puncture tests, and stability testing revealed the need for light- and moisture-resistant packaging. The formulations selected based on the obtained results will be further investigated on the way to create a transdermal alternative to agomelatine oral tablets and increase the effectiveness of depression treatment.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126572"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2026-01-05DOI: 10.1016/j.ijpharm.2026.126571
Mais M. Saleh , Nowar Alsarayreh , Nour Aladaileh , Yousef Ijjeh , Dana A. Alqudah , Helen Al-Zain , Hatim S. Alkhatib , Marzouq Amarin , Maram Abdeljaleel , Rand Murshidi , Walhan Alshaer
Liposomes have gained a great attention in cosmeceutical dermal delivery. These nanolipid carriers can load numerous actives, and when applied on skin they can form transparent film that reduces transepidermal water loss (TEWL), i.e., increases skin hydration. This work aims were to investigate the feasibility of forming liposomal tocopherol phosphate (TPLP) and to evaluate their ex vivo skin penetration profiles, skin hydration, in vitro cell migration effects, and in vivo wound healing effects. The TPLP formulations were prepared by thin film hydration method. In vitro release testing (IVRT) and ex-vivo skin penetration studies were performed in Franz diffusion cells. The migration effect was performed using in vitro scratch assay on human dermal fibroblast (HDF). The wound healing properties were studied in vivo on mouse excisional wound model. The TPLP-7 formulation was physically stable with small size, and low PDI. The flux of TP from TPLP-7 was 218.74 ± 131.74 and 151.84 ± 38.72 µg/cm2/min, for IVRT and ex-vivo penetration testing, respectively. The TEWL measurements confirmed superior skin hydrating effects following TPLP-7 application compared with free TP control (pH 8). The TPLP-7 also showed good skin tolerability and notable antioxidant activity. The TPLP-7 significantly promoted HDF migration and accelerated scratch closure. These findings were consistent with the in vivo results, where TPLP-7 and free TP enhanced the wound closure similar to the positive control. This study highlights the potential use of TP liposomes as a promising candidate for cosmeceutical and wound healing applications.
{"title":"Design of liposomal tocopherol phosphate for dermal applications","authors":"Mais M. Saleh , Nowar Alsarayreh , Nour Aladaileh , Yousef Ijjeh , Dana A. Alqudah , Helen Al-Zain , Hatim S. Alkhatib , Marzouq Amarin , Maram Abdeljaleel , Rand Murshidi , Walhan Alshaer","doi":"10.1016/j.ijpharm.2026.126571","DOIUrl":"10.1016/j.ijpharm.2026.126571","url":null,"abstract":"<div><div>Liposomes have gained a great attention in cosmeceutical dermal delivery. These nanolipid carriers can load numerous actives, and when applied on skin they can form transparent film that reduces transepidermal water loss (TEWL), i.e., increases skin hydration. This work aims were to investigate the feasibility of forming liposomal tocopherol phosphate (TPLP) and to evaluate their <em>ex vivo</em> skin penetration profiles, skin hydration, <em>in vitro</em> cell migration effects, and <em>in vivo</em> wound healing effects. The TPLP formulations were prepared by thin film hydration method. <em>In vitro</em> release testing (IVRT) and <em>ex-vivo</em> skin penetration studies were performed in Franz diffusion cells. The migration effect was performed using <em>in vitro</em> scratch assay on human dermal fibroblast (HDF). The wound healing properties were studied <em>in vivo</em> on mouse excisional wound model. The TPLP-7 formulation was physically stable with small size, and low PDI. The flux of TP from TPLP-7 was 218.74 ± 131.74 and 151.84 ± 38.72 µg/cm<sup>2</sup>/min, for <em>IVRT</em> and <em>ex-vivo</em> penetration testing, respectively. The TEWL measurements confirmed superior skin hydrating effects following TPLP-7 application compared with free TP control (pH 8). The TPLP-7 also showed good skin tolerability and notable antioxidant activity. The TPLP-7 significantly promoted HDF migration and accelerated scratch closure. These findings were consistent with the <em>in vivo</em> results, where TPLP-7 and free TP enhanced the wound closure similar to the positive control. This study highlights the potential use of TP liposomes as a promising candidate for cosmeceutical and wound healing applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126571"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2026-01-06DOI: 10.1016/j.ijpharm.2026.126566
Shuang Chen , Xuan He , Yunxia Ye , Shiyu Zhu , Zhipeng Tian , Mingrui Yang , Shuochen Pang , Man Li , Rong Guo , Qin He
Chemotherapy plays an irreplaceable role in the clinical treatment of malignant tumors, yet drug resistance remains a major cause of suboptimal therapeutic outcomes. Ferroptosis, a regulated cell death modality, offers a promising therapeutic strategy, as the chemotherapy-resistant tumor cells exhibit heightened sensitivity to this process. Combining chemotherapeutics with ferroptosis-inducing agents thus represents a viable approach to overcome chemotherapy resistance. The accumulation of polyunsaturated fatty acids (PUFAs) is an important factor contributing to the increase of lipid peroxides and triggering ferroptosis, and arachidonic acid (AA) is a typical type of PUFAs. Based on that, we designed an amphiphilic polymer dextran-AA (Dex-AA), and constructed an AA-functionalized micelle DA through its self-assembly, with the chemotherapeutic drug doxorubicin (DOX) encapsulated within the cores. The obtained micelle DA/DOX induced ferroptosis by promoting lipid peroxidation, which significantly enhanced the cytotoxicity of DOX against DOX-resistant tumor cells. Meanwhile, DA/DOX synergistically maintained high intracellular drug levels via an “open-source throttling” strategy by both promoting uptake via the enhanced membrane fluidity and inhibiting ATP-dependent efflux through ROS-induced mitochondrial damage/ATP depletion. In vitro studies confirmed the excellent efficacy of DA/DOX in both 4T1 and MCF-7/ADR cells. Furthermore, in the breast cancer mouse model, DA/DOX exhibited superior antitumor effects compared to the long-circulating DOX liposomes (Lip/DOX). This study presents a novel strategy based on ferroptosis to overcome chemotherapy resistance of breast cancer, which is of great significance.
化疗在恶性肿瘤的临床治疗中发挥着不可替代的作用，但耐药性仍然是导致治疗效果不理想的主要原因。铁下垂是一种受调控的细胞死亡方式，提供了一种有希望的治疗策略，因为化疗耐药的肿瘤细胞对这一过程表现出更高的敏感性。因此，将化疗药物与诱导铁中毒的药物联合使用是克服化疗耐药性的可行方法。多不饱和脂肪酸（PUFAs）的积累是导致脂质过氧化物增加和引发铁下垂的重要因素，花生四烯酸（AA）是一种典型的PUFAs。在此基础上，我们设计了一种两亲性聚合物葡聚糖- aa (Dex-AA)，并通过其自组装构建了一个aa功能化的胶团DA，并将化疗药物多柔比星（DOX）封装在胶团核心内。获得的胶束DA/DOX通过促进脂质过氧化作用诱导铁下垂，从而显著增强DOX对DOX耐药肿瘤细胞的细胞毒性。同时，DA/DOX通过“开源节流”策略，通过增强膜流动性促进摄取和通过ros诱导的线粒体损伤/ATP耗竭抑制ATP依赖性外溢，协同维持高细胞内药物水平。体外研究证实了DA/DOX对4T1和MCF-7/ADR细胞的良好疗效。此外，在乳腺癌小鼠模型中，与长循环DOX脂质体（Lip/DOX）相比，DA/DOX表现出更好的抗肿瘤作用。本研究提出了一种基于铁下垂克服乳腺癌化疗耐药的新策略，具有重要意义。
{"title":"Arachidonic acid-functionalized micelle induces ferroptosis of tumor cells to overcome chemotherapy resistance for breast cancer therapy","authors":"Shuang Chen , Xuan He , Yunxia Ye , Shiyu Zhu , Zhipeng Tian , Mingrui Yang , Shuochen Pang , Man Li , Rong Guo , Qin He","doi":"10.1016/j.ijpharm.2026.126566","DOIUrl":"10.1016/j.ijpharm.2026.126566","url":null,"abstract":"<div><div>Chemotherapy plays an irreplaceable role in the clinical treatment of malignant tumors, yet drug resistance remains a major cause of suboptimal therapeutic outcomes. Ferroptosis, a regulated cell death modality, offers a promising therapeutic strategy, as the chemotherapy-resistant tumor cells exhibit heightened sensitivity to this process. Combining chemotherapeutics with ferroptosis-inducing agents thus represents a viable approach to overcome chemotherapy resistance. The accumulation of polyunsaturated fatty acids (PUFAs) is an important factor contributing to the increase of lipid peroxides and triggering ferroptosis, and arachidonic acid (AA) is a typical type of PUFAs. Based on that, we designed an amphiphilic polymer dextran-AA (Dex-AA), and constructed an AA-functionalized micelle DA through its self-assembly, with the chemotherapeutic drug doxorubicin (DOX) encapsulated within the cores. The obtained micelle DA/DOX induced ferroptosis by promoting lipid peroxidation, which significantly enhanced the cytotoxicity of DOX against DOX-resistant tumor cells. Meanwhile, DA/DOX synergistically maintained high intracellular drug levels via an “open-source throttling” strategy by both promoting uptake via the enhanced membrane fluidity and inhibiting ATP-dependent efflux through ROS-induced mitochondrial damage/ATP depletion. In vitro studies confirmed the excellent efficacy of DA/DOX in both 4T1 and MCF-7/ADR cells. Furthermore, in the breast cancer mouse model, DA/DOX exhibited superior antitumor effects compared to the long-circulating DOX liposomes (Lip/DOX). This study presents a novel strategy based on ferroptosis to overcome chemotherapy resistance of breast cancer, which is of great significance.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126566"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2025-12-30DOI: 10.1016/j.ijpharm.2025.126549
Zhipeng Xu, Jinku Xu
Polyester drug-loaded microspheres represent a widely utilised sustained-release drug delivery system in clinical practice, whose efficient development relies upon systematic understanding of material design, controllable preparation, and in vivo behaviour prediction. However, existing reviews predominantly focus on singular dimensions, lacking a comprehensive perspective spanning the entire chain from “laboratory design to industrial production to clinical performance prediction”. To address this, this paper pioneers the adoption of a “laboratory- Fabrication–Clinical application” framework to systematically review recent advances in polyester microspheres. Firstly, it thoroughly analyses rational design strategies for regulating drug release kinetics based on polyester matrix properties (such as LA:GA ratio, molecular weight, end groups, crystallinity, etc.), alongside cutting-edge controlled-release techniques including surface modification, composite carriers, and core–shell/porous structures. Secondly, it assesses the industrialisation potential and bottlenecks of various preparation techniques, emphasising the critical influence of process parameters on microsphere structure and release mechanisms. Finally, it focuses on challenges in establishing in vivo-in vitro correlations, exploring their mechanistic foundations, strategies for integrating physiological pharmacokinetic models, and cutting-edge approaches to addressing translational hurdles. This review not only provides a comprehensive technical summary but also offers a clear roadmap for the strategic development of polyester drug-loaded microspheres from concept to product.
{"title":"Research progress and prospect of preparation and long-acting drug release of polyester drug-loaded microspheres","authors":"Zhipeng Xu, Jinku Xu","doi":"10.1016/j.ijpharm.2025.126549","DOIUrl":"10.1016/j.ijpharm.2025.126549","url":null,"abstract":"<div><div>Polyester drug-loaded microspheres represent a widely utilised sustained-release drug delivery system in clinical practice, whose efficient development relies upon systematic understanding of material design, controllable preparation, and in vivo behaviour prediction. However, existing reviews predominantly focus on singular dimensions, lacking a comprehensive perspective spanning the entire chain from “laboratory design to industrial production to clinical performance prediction”. To address this, this paper pioneers the adoption of a “laboratory- Fabrication–Clinical application” framework to systematically review recent advances in polyester microspheres. Firstly, it thoroughly analyses rational design strategies for regulating drug release kinetics based on polyester matrix properties (such as LA:GA ratio, molecular weight, end groups, crystallinity, etc.), alongside cutting-edge controlled-release techniques including surface modification, composite carriers, and core–shell/porous structures. Secondly, it assesses the industrialisation potential and bottlenecks of various preparation techniques, emphasising the critical influence of process parameters on microsphere structure and release mechanisms. Finally, it focuses on challenges in establishing in vivo-in vitro correlations, exploring their mechanistic foundations, strategies for integrating physiological pharmacokinetic models, and cutting-edge approaches to addressing translational hurdles. This review not only provides a comprehensive technical summary but also offers a clear roadmap for the strategic development of polyester drug-loaded microspheres from concept to product.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126549"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2025-12-17DOI: 10.1016/j.ijpharm.2025.126514
Akanksha Mahajan , Gajanand Sharma , Sarah R. Dennison , Kamalinder K. Singh , Bhupinder Singh , Om Prakash Katare
This work reports the first systematic formulation strategy guided by Quality-by-Design (QbD) principles to create an ultra-deformable ethosomes (UDEs) based nanocarrier for luliconazole (LCZ). The approach addresses the long-standing barriers of poor solubility, limited skin penetration, and rapid drug clearance in dermatophytosis therapy. A Box-Behnken design identified the optimal composition, including phospholipid (PL 90G), Span® 20, and ethanol: propylene glycol, yielding highly elastic nanosized vesicles (particle size 196.97 ± 1.57 nm; polydispersity index 0.158 ± 0.03) with exceptional percent drug entrapment (91.0%) and sustained release (62% over 12 h). Incorporation into a Carbopol 980 gel conferred favourable shear-thinning behaviour, enhanced spreadability, and superior texture as compared to a marketed 1% LCZ cream (MKT-LF). Ex vivo permeation across rat skin demonstrated a 2.4-fold higher flux and 11.3-fold greater cutaneous deposition than MKT-LF, attributed to synergistic vesicle deformability and ethanol-induced fluidization of stratum corneum. LCZ-UDEs demonstrated deep epidermal penetration of intact fluorescently labelled vesicles. Dermatokinetic profiling revealed a 3.4-fold increase in epidermal AUC0-12, prolonged half-life, and delayed Tmax, indicating enhanced skin retention. Antifungal assays demonstrated a two-fold reduction in MIC, and rapid fungicidal kinetics against Trichophyton rubrum compared with LCZ solution and MKT-LF. Biocompatibility studies validated >90% HaCaT cell viability, no haemolysis, and absence of dermal irritation. Sustained intradermal LCZ levels minimized sub-therapeutic exposure that drives fungal resistance. By uniting nanoscale vesicle engineering, ethanol-enhanced skin permeation, and QbD-optimized composition, this study delivers a stable, safe, and efficacious topical nanoplatform with potential to transform dermatophytosis management and mitigate antifungal resistance.
{"title":"Quality-by-design-steered development of luliconazole-loaded ultra-deformable ethosomes for topical delivery: improved dermatokinetics and antifungal activity","authors":"Akanksha Mahajan , Gajanand Sharma , Sarah R. Dennison , Kamalinder K. Singh , Bhupinder Singh , Om Prakash Katare","doi":"10.1016/j.ijpharm.2025.126514","DOIUrl":"10.1016/j.ijpharm.2025.126514","url":null,"abstract":"<div><div>This work reports the first systematic formulation strategy guided by Quality-by-Design (QbD) principles to create an ultra-deformable ethosomes (UDEs) based nanocarrier for luliconazole (LCZ). The approach addresses the long-standing barriers of poor solubility, limited skin penetration, and rapid drug clearance in dermatophytosis therapy. A Box-Behnken design identified the optimal composition, including phospholipid (PL 90G), Span® 20, and ethanol: propylene glycol, yielding highly elastic nanosized vesicles (particle size 196.97 ± 1.57 nm; polydispersity index 0.158 ± 0.03) with exceptional percent drug entrapment (91.0%) and sustained release (62% over 12 h). Incorporation into a Carbopol 980 gel conferred favourable shear-thinning behaviour, enhanced spreadability, and superior texture as compared to a marketed 1% LCZ cream (MKT-LF). <em>Ex vivo</em> permeation across rat skin demonstrated a 2.4-fold higher flux and 11.3-fold greater cutaneous deposition than MKT-LF, attributed to synergistic vesicle deformability and ethanol-induced fluidization of stratum corneum. LCZ-UDEs demonstrated deep epidermal penetration of intact fluorescently labelled vesicles. Dermatokinetic profiling revealed a 3.4-fold increase in epidermal AUC<sub>0-12</sub>, prolonged half-life, and delayed T<sub>max</sub>, indicating enhanced skin retention. Antifungal assays demonstrated a two-fold reduction in MIC, and rapid fungicidal kinetics against <em>Trichophyton rubrum</em> compared with LCZ solution and MKT-LF. Biocompatibility studies validated >90% HaCaT cell viability, no haemolysis, and absence of dermal irritation. Sustained intradermal LCZ levels minimized sub-therapeutic exposure that drives fungal resistance. By uniting nanoscale vesicle engineering, ethanol-enhanced skin permeation, and QbD-optimized composition, this study delivers a stable, safe, and efficacious topical nanoplatform with potential to transform dermatophytosis management and mitigate antifungal resistance.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126514"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2026-01-06DOI: 10.1016/j.ijpharm.2025.126531
Rui Ran, Yayuan Liu, Huile Gao, Qifang Kuang, Qianyu Zhang, Jie Tang, Kai Huang, Xiaoxiao Chen, Zhirong Zhang, Qin He
{"title":"Corrigendum to “Enhanced gene delivery efficiency of cationic liposomes coated with PEGylated hyaluronic acid for anti P-glycoprotein siRNA: A potential candidate for overcoming multi-drug resistance”. [Int. J. of Pharm. 477 (2014) 590–600]","authors":"Rui Ran, Yayuan Liu, Huile Gao, Qifang Kuang, Qianyu Zhang, Jie Tang, Kai Huang, Xiaoxiao Chen, Zhirong Zhang, Qin He","doi":"10.1016/j.ijpharm.2025.126531","DOIUrl":"10.1016/j.ijpharm.2025.126531","url":null,"abstract":"","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126531"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号